Myocardial infarctions affect 1.5 million Americans annually and represent the leading cause of death in those over the age of 30. Survivors are at risk of second infarctions as well as decreased cardiac function and progression to heart failure. Ventricular function is a major predictor of prognosis in survivors. Patients undergoing coronary artery bypass graft (CABG) surgery also experience myocardial ischemia and the extent of damage predicts long-term survival. A critical unmet need is the development of therapies that will preserve myocardial tissue after ischemia and reperfusion. We have identified a class of small molecules that are highly protective in the isolated perfused rat heart subjected to global no-flow ischemia and reperfusion, as well as in the in vivo rabbit heart surgical model of ischemia and reperfusion. Radical Therapeutix, Inc. (RTX) has developed a novel compound, Sul-car, which we now propose to test in the porcine model as proof of concept. If the large-animal studies demonstrate efficacy, we will embark on the next steps of drug development (final medicinal chemistry, scale-up of synthesis, and pharmacokinetics and toxicology studies) in preparation for human clinical trials. The primary end-point of this Phase I SBIR project is to establish whether Sul-car can reduce infarct size or stunning in a porcine model of ischemia/reperfusion. PUBLIC HEALTH RELEVANCE: This proposal is designed to test whether a new small molecule agent can reduce the injury to the heart after ischemia and reperfusion ("heart attack"). The study will be conducted using pigs, which are the best model for predicting whether an agent is likely to be successful in humans. If the study is successful, we will proceed with efforts to ready the drug candidate for human clinical trials.